Sulfonamides as new hydrogen atom transfer (HAT) catalysts for photoredox allylic and benzylic C-H arylations

Article abstract of DOI:10.1039/c7cc09457d

A catalytic amount of a sterically and electronically tuned diarylsulfonamide promoted allylic and benzylic C-H arylations in cooperation with a visible light photoredox catalyst. This is the first example of the catalytic use of a sulfonamidyl radical to promote the hydrogen atom transfer process.

Full text of DOI:10.1039/c7cc09457d

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Sulfonamides as new hydrogen atom transfer (HAT) catalysts for
photoredox allylic and benzylic C-H arylations
Received 00th
January 20xx,
Hirotaka Tanaka,a Kentaro Sakai,a Atsushi Kawamura,a Kounosuke Oisaki,*a and Motomu Kanai*a
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A catalytic amount of a sterically and electronically tuned of complex molecules is problematic. On the other hand, a
diarylsulfonamide promoted allylic and benzylic C-H arylations in HAT catalyst with a weak BDE (e.g., for iPr3SiSH, BDE (S-H) = 87
cooperation with a visible light photoreodox catalyst. This is the kcal/mol5c) has limited applicability to unactivated sp3 C-H
first example of the catalytic use of a sulfonamidyl radical to bonds. Therefore, a structurally new HAT catalyst with an
promote the hydrogen atom transfer process.
easily and flexibly tunable BDE is highly desired (Figure 1a).
Here we report the development of a PC-HAT hybrid
system using a sulfonamide as a new HAT catalyst for allylic
and benzylic C-H arylations.
Synthetic methods using a photoredox catalyst (PC) have
greatly advanced in recent years.1 Under such circumstances,
sp3 C–H functionalization promoted by hybrid catalysis relying
on a PC and hydrogen atom transfer (HAT) process has
attracted much attention.2 The HAT process is more
advantageous than conventional sp3 C-H activations3 with
respect to the high chemo- and site-selectivity achieved
without protecting groups, the high atom-economy, and the
applicability of the mild, green and metal-free conditions with
high energy efficiency. Therefore, the PC-HAT hybrid system
has inspired many synthetic chemists to establish streamlined
and intuitive synthetic routes and late-stage functionalizations
of complex molecules.4
Several examples of mild sp3 C-H functionalization
promoted by catalytic amounts of HAT components, such as
thiols,5 quinuclidine,6 benzoic acid7 and N-hydroxy
compounds,8 with cooperative use of PCs were recently
reported. The utility of these reactions, however, is highly
dependent on the strength of the inherent bond dissociation
energy (BDE). A HAT catalyst with a strong BDE (e.g., for
benzoic acid, BDE(O-H) = 110 kcal/mol7) often randomly
cleaves multiple sp3 C-H bonds of both the substrate and
solvent. Therefore, its application for selective transformation
Figure 1. (a) BDE(X-H) of representative HAT catalysts and
solvents. (b) Calculated BDE(N-H) of sulfonamides.9
Our survey of many possible HAT structures revealed that
the BDE(N-H) values of sulfonamides are within the proper
range (90-100 kcal/mol,9,10 Figure 1b). Additionally, the BDE
values can be properly adjusted by changing the sulfur or
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nitrogen substituents. The acidity of their N-H bonds is also suitable HAT catalyst, comprising
important for acquiring HAT activity, because prior electron-donating aryl sulfone and strongly electron-
deprotonation makes sulfonamides susceptible to single- withdrawing aniline. The BDE(N-H) value of was calculated to
electron oxidation to produce active sulfonamidyl radicals.10,11 be 95 kcal/mol.9 We also found that the cation effect of the
Furthermore, ulfonamides are very easy to synthesize, base used for the deprotonation of was crucial. Among the
a sterically-hindered
4
s
4
allowing for accelerated catalyst screening. There are no bases tested, potassium bases worked efficiently. For ease of
reports of the catalytic use of sulfonamidyl radical precursors handling, we selected K2CO3 (see SI). In the presence of 1 mol%
in a PC-HAT hybrid system,11 probably because of their of fac-Ir(Fppy)3 (Fppy = 2-(4,6-difluorophenyl)pyridine), 20
tendency to form C-N bonds.12
mol% each of 4 and K2CO3 under blue LED irradiation, the
desired C-H arylation proceeded to afford 3a in 12% yield
(entry 1). The reaction yield was improved to 42% by using 2
mol% of the PC (entry 2). We hypothesized that the low
catalyst turnover was due to insufficient deprotonation
resulting from the poor solubility of K2CO3 in acetone.
CN
1
Ir(Fppy)3
NC
1 eq
+
HAT catalyst 4
Therefore, we applied a premixing protocol of
4 and K2CO3 for
K2CO3
acetone, 40 o
C
NC
30 min before starting the reaction, which improved the yield
(79%, entry 3). When the amounts of HAT and base were
decreased to 10 mol% each, the yield was further increased
(91%, entry 4). Several control experiments conducted to
clarify the reaction mechanism demonstrated that light, base,
2a
3a
Blue LED, 24 h
H
5 eq
yielda
(%)
Ir(Fppy)3 HAT 4 K2CO3
(mol%) (mol%) (mol%)
entry
light
comment
PC, and HAT catalyst
reaction (entries 5-8).
4 were all essential for promoting the
1
2
3
4
1
2
2
2
20
20
20
10
20
20
20
10
ON
ON
ON
ON
12
42
79
91
base/HAT premix
base/HAT premix
Next, we investigated the substrate scope and limitations
(Table 2) under the optimal conditions (Table 1, entry 4).
5
6
7
8
2
2
2
0
10
10
0
10
0
OFF
ON
ON
ON
0
0
0
0
base/HAT premix
base/HAT premix
base/HAT premix
base/HAT premix
Cyclohexene (2a), cyclopentene (2b) and cycloheptene (2c
produced the C-H arylation products 3a 3c, respectively, in
moderate to high yield. Allylic C-H arylation of α-pinene (2d
)
-
10
10
)
10
was promoted with high regioselectivity (>10:1) (3d). Cyclic
ethers such as phthalane (2e) and isochroman (2f), were
efficiently converted to 3e and 3f, respectively. Acyclic benzylic
ethers were also found to be good substrates. Dibenzyl ether
a Yield was determined by 1H NMR in the presence of nitromethane or
1,1,2,2-tetrachloroethane as internal standards.
sterically
F
F
(
2g), methyl benzyl ethers
butyldimethylsilyl ethers (2j 2n) all produced the desired C-H
arylation products 3g 3n in moderate to high yield. Even
unprotected benzyl alcohols 2o 2r could be converted to the
corresponding dibenzyl alcohols 3o 3r, although the yield was
(2h and 2i), and tert-
hindered aryl
CF3
-
N
Ir
-
O2
S
F
F
-
N
CF3
-
N
F
N
F
H
moderate due to the oxidative side- reaction forming the
corresponding ketones or aldehydes. Arylation of p-
isopropylanisole (2s) and p-ethylanisole (2t) proceeded in only
21% and 3% yield, respectively (3s and 3t). In general, both the
stability of the carbon radical and steric hindrance around the
reactive C-H bond markedly affected the chemical yield. An
electron-donating substituent (such as methoxy groups) on the
benzene ring improved the chemical yield, but a sterically
demanding electron-withdrawing group (such as ortho-
halogens) significantly decreased the yield.
electron-
deficient aryl
HAT catalyst 4
BDE(N H) = 95 kcal / mol
fac- Ir(Fppy)3
Table 1. Optimization and control experiment
5a,c
Allylic C-H arylation with 1,4-dicyanobenzene (
1
)
was
used as a model reaction to identify suitable sulfonamide HAT
catalysts (Table 1). Structural screening of a variety of
molecules (see ESI) led us to identify diarylsulfonamide
4 as a
2 | J. Name., 2012, 00, 1-3
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sulfonamidyl radical from deprotonated
Ⅲ
electron oxidation. Initial reduction of 1 by Ir to produce Ir
4 through one-
*
Ⅳ
as reported by MacMillan5a,c was not operative, because our
system utilizes a lower reduction potential of the excited
*
Ⅲ
13
Ir(Fppy)3 species (Ir /Ir : -1.43 V) than that of the Ir(ppy)3
Ⅳ
*
Ⅲ
used in their system (Ir /Ir : -1.73V), resulting in insufficient
Ⅳ
−
Ⅱ
reduction of
1 (1･ /1: -1.64 V). On the other hand, the Ir
species generated after oxidation of deprotonated
Ⅱ
reduction potential (Ir /Ir : -2.11 V). Therefore, one-electron
4
has a high
Ⅲ
Ⅱ
1 is promoted by Ir to regenerate the Ir species,
Ⅲ
reduction of
which completes the photocatalytic cycle.15 The thus-
generated sulfonamidyl radical enters the HAT process to
produce carbon radicals from substrate
reduced to afford the desired C-H arylation product
the elimination of a CN anion. The eliminated CN anion acts as
a base to deprotonate and close the HAT catalytic cycle.
2, which react with the
1
3
after
4
Scheme 1. Proposed reaction mechanism
In summary, we demonstrated that sulfonamides can
function as novel HAT catalysts applicable to allylic or benzylic
C-H arylations with the cooperation of a PC. The BDE(N-H) of
sulfonamide
4 was calculated to be 95 kcal/mol, suggesting its
Table 2. Allylic or benzylic C-H arylation catalyzed by the PC-
applicability to selective HAT processes avoiding random
activation of strong C-H bonds in organic molecules. Moreover,
structures of sulfonamide HAT catalysts are easily tunable,
allowing for a possibility of facile optimization depending on
substrates and reaction patterns, respectively. Further
improvement of the catalyst turnover, selectivity and
substrate generality is ongoing in our laboratory.
sulfonamide HAT hybrid system
Finally, we applied this PC-HAT hybrid system to late-stage
functionalization of prasterone (2u). The reaction proceeded
smoothly in high yield and with high regioselectivity (82%,
>10:1) to produce arylated product 3u without affecting the
unprotected hydroxy or carbonyl groups.
A plausible mechanism for the C-H arylation is proposed in
Conflicts of interest
Scheme 1 according to the redox potentials of the PC and HAT
Ⅲ
catalyst 4. First, the ground-state PC (Ir ) is excited by visible
There are no conflicts to declare.
*
Ⅲ
light to produce the Ir
species, which has an oxidation
potential (Ir /Ir : +0.5 V)13 greater than that of deprotonated
(N
/N−: +0.47 V),14 allowing for the generation of an active
*
Ⅲ
Ⅱ
Notes and references
4
･
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, 6796.
4 was determined by
14 The redox potential of deprotonated
cyclic voltammetry. See ESI for details.
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4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C7CC09457D
TOC:
Sulfonamides function as novel hydrogen atom
transfer catalysts applicable to C-H arylations with a
photoredox catalyst for the first time.